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目的探讨β整合素家族成员在儿童急性T淋巴细胞白血病(T-ALL)的表达及临床意义。方法收集22例初诊T-ALL患儿和21例对照(非恶性血液病患者和骨髓移植供者)的骨髓标本,采用实时荧光定量PCR方法,检测β整合素家族各成员的m RNA表达;并利用整合素抑制剂精氨酸-甘氨酸-天冬氨酸(RGD)肽作用于Jurkat细胞,采用CCK 8法和流式细胞术检测Jurkat细胞生存率和凋亡情况。结果与对照组相比,T-ALL患儿的整合素β_2、β_3、β_5的m RNA表达水平显著下调(P<0.05)。在外周血白细胞计数<100×10~9/L、第33天骨髓不缓解或MRD阳性的T-ALL患儿中,整合素β_3表达水平较高(P<0.05);复发T-ALL患儿整合素β_5的表达高于无复发T-ALL患儿(P<0.05)。整合素β3高表达T-ALL患儿的EFS率、OS率均低于β_3低表达者(P<0.05)。与未处理组比较,RGD肽处理的Jurkat细胞生存率较低、凋亡率均高(P<0.05)。结论β整合素可能通过影响细胞的增殖和凋亡而影响T-ALL的发生发展,整合素β_5的表达与T-ALL复发风险密切相关,整合素β_3的表达与T-ALL患儿治疗反应及预后密切相关。
Objective To investigate the expression and clinical significance of β integrin family members in children with acute T-lymphoblastic leukemia (T-ALL). Methods Twenty-two newly diagnosed T-ALL infants and 21 controls (non-hematologic malignancies and bone marrow donor) were collected for bone marrow biopsy. Real-time fluorescence quantitative PCR was used to detect the m RNA expression in each member of the β-integrin family. Jurkat cells were treated with the integrin inhibitor arginine-glycine-aspartate (RGD) peptide. The survival rate and apoptosis of Jurkat cells were detected by CCK8 assay and flow cytometry. Results Compared with the control group, the expression of integrin β 2, β 3 and β 5 m RNA in T-ALL children was significantly decreased (P <0.05). The expression of integrin β 3 was higher in children with T-ALL whose peripheral blood leucocyte count was less than 100 × 10 ~ 9 / L on the 33rd day and bone marrow did not relieve or MRD positive on the 33rd day (P <0.05) The expression of integrin β_5 was higher in children with no recurrence of T-ALL (P <0.05). The EFS rate and OS rate of integrin β3-overexpressing T-ALL children were both lower than those with low β_3 expression (P <0.05). Compared with the untreated group, the survival rate of Jurkat cells treated with RGD peptide was lower and the apoptosis rate was higher (P <0.05). Conclusion β-integrin may affect the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrinβ_5 is closely related to the risk of T-ALL recurrence. The expression of integrinβ_3 is correlated with the response to T-ALL and The prognosis is closely related.